Effect of tamoxifen on regulation of viral replication and human immunodeficiency virus (HIV) long terminal repeat-directed transcription in cells chronically infected with HIV-1.
The protein kinase C (PKC) activator phorbol myristate acetate (PMA) was used to upregulate viral replication in a clone of promonocytic cells chronically infected with human immunodeficiency virus (HIV)-1. Induction of virus could be inhibited by the triphenylethylene anti-estrogen tamoxifen at concentrations that had minimal effects on cellular DNA synthetic responses and cell cycle kinetics. This effect correlated with tamoxifen's ability to block PMA-mediated enhancement of HIV-promoter-driven transactivation in cells of monocyte and CD4+ T-lymphocyte lineages. No interference with a primary infection was noted. Tamoxifen's mechanism of action may relate both to its capacity to inhibit PKC and to consensus sequences for gonadal steroid responsive elements in the HIV long terminal repeat, as it was able to partially inhibit another HIV activator, 5-azacytidine, which does not modulate PKC function. The finding that regulation of HIV in a model for low-level chronic or latent infection is amenable to a nonimmunosuppressive steroid antagonist may suggest approaches to pharmacologic intervention early in HIV infection.
Laurence
J
J
Laboratory for AIDS Virus Research, New York Hospital, NY.
Cooke
H
H
Sikder
S K
SK
D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D006678:HIV / Q000187:drug effects / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D066298:In Vitro Techniques; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
D014157:Transcription Factors; D013629:Tamoxifen; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate